title: Arteriolar niches maintain haematopoietic stem cell quiescence.
abstract: Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant three-dimensional associations in the mouse bone marrow among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal bone marrow. These arterioles are ensheathed exclusively by rare NG2 (also known as CSPG4)(+) pericytes, distinct from sinusoid-associated leptin receptor (LEPR)(+) cells. Pharmacological or genetic activation of the HSC cell cycle alters the distribution of HSCs from NG2(+) periarteriolar niches to LEPR(+) perisinusoidal niches. Conditional depletion of NG2(+) cells induces HSC cycling and reduces functional long-term repopulating HSCs in the bone marrow. These results thus indicate that arteriolar niches are indispensable for maintaining HSC quiescence.
authors.affiliation: 1] Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA [2] Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kunisaki
authors.forename: Ingmar
authors.initials: I
authors.lastname: Bruns
authors.forename: Christoph
authors.initials: C
authors.lastname: Scheiermann
authors.forename: Jalal
authors.initials: J
authors.lastname: Ahmed
authors.forename: Sandra
authors.initials: S
authors.lastname: Pinho
authors.forename: Dachuan
authors.initials: D
authors.lastname: Zhang
authors.forename: Toshihide
authors.initials: T
authors.lastname: Mizoguchi
authors.forename: Qiaozhi
authors.initials: Q
authors.lastname: Wei
authors.forename: Daniel
authors.initials: D
authors.lastname: Lucas
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ito
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Mar
authors.forename: Aviv
authors.initials: A
authors.lastname: Bergman
authors.forename: Paul S
authors.initials: PS
authors.lastname: Frenette
mesh_terms: D000818:Animals; D001160:Arterioles / Q000166:cytology*; D001853:Bone Marrow / Q000098:blood supply; D002455:Cell Division; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D064231:Nestin / Q000378:metabolism; D055153:Stem Cell Niche
chemical_list: C577485:Nes protein, mouse; D064231:Nestin